Abstract
Microcystin-LR (MC-LR) is an extremely poisonous cyanotoxin that poses a threat to ecosystems and human health. MC-LR has been reported as an enterotoxin. The objective of this study was to determine the effect and the mechanism of subchronic MC-LR toxicity on preexisting diet-induced colorectal damage. C57BL/6J mice were given either a regular diet or a high-fat diet (HFD) for 8 weeks. After 8 weeks of feeding, animals were supplied with vehicle or 120 μg/L MC-LR via drinking water for another 8 weeks, and their colorectal were stained with H&E to detect microstructural alterations. Compared with the CT group, the HFD and MC-LR + HFD-treatment group induced a significant weight gain in the mice. Histopathological findings showed that the HFD- and MC-LR + HFD-treatment groups caused epithelial barrier disruption and infiltration of inflammatory cells. The HFD- and MC-LR + HFD-treatment groups raised the levels of inflammation mediator factors and decreased the expression of tight junction-related factors compared to the CT group. The expression levels of p-Raf/Raf and p-ERK/ERK in the HFD- and MC-LR + HFD-treatment groups were significantly increased compared with the CT group. Additionally, treated with MC-LR + HFD, the colorectal injury was further aggravated compared with the HFD-treatment group. These findings suggest that by stimulating the Raf/ERK signaling pathway, MC-LR may cause colorectal inflammation and barrier disruption. This study suggests that MC-LR treatment may exacerbate the colorectal toxicity caused by an HFD. These findings offer unique insights into the consequences and harmful mechanisms of MC-LR and provide strategies for preventing and treating intestinal disorders.